【结 构 式】 |
【分子编号】65002 【品名】2-(benzyloxy)-4-[2-chloro-4-(difluoromethoxy)phenyl]-3-nitropyridine; benzyl 4-[2-chloro-4-(difluoromethoxy)phenyl]-3-nitro-2-pyridinyl ether 【CA登记号】 |
【 分 子 式 】C19H13ClF2N2O4 【 分 子 量 】406.7728064 【元素组成】C 56.1% H 3.22% Cl 8.72% F 9.34% N 6.89% O 15.73% |
合成路线1
该中间体在本合成路线中的序号:(VI)Nitration of 2,4-dihydroxypyridine (I) affords the 3-nitro derivative (II). Selective chlorination of the 4-hydroxy group of (II) is accomplished by treatment of the cycloheptylamine salt of (II) with POCl3 to furnish 4-chloro-2-hydroxy-3-nitropyridine (III). The 2-hydroxy group of (III) is then protected as the benzyl ether (IV) using benzyl bromide in the presence of silver carbonate. Suzuki coupling of protected chloropyridine (IV) with 2-chloro-4-(difluoromethoxy)phenylboronic acid (V) leads to the phenylpyridine derivative (VI). The O-benzyl group of (VI) is then removed with trifluoroacetic acid, and the resultant 2-hydroxypyridine (VII) is further chlorinated by means of POCl3, yielding (VIII). Displacement of the 2-chloro substituent of (VIII) with 1-cyclobutylethylamine (IX) in refluxing acetonitrile furnishes the 2-amino-3-nitropyridine (X). Subsequent nitro group reduction in (X) employing sodium dithionite and ammonium hydroxide leads to diamine (XI). This is finally cyclized to the desired imidazopyridine upon heating at reflux with propionic acid.
【1】 Arvanitis, A.G.; Rescinito, J.T.; Arnold, C.R.; Wilde, R.G.; Cain, G.A.; Sun, J.H.; Yan, J.-S.; Teleha, C.A.; Fitzgerald, L.W.; McElroy, J.; Zaczek, R.; Hartig, P.R.; Grossman, S.; Arneric, S.P.; Gilligan, P.J.; Olson, R.E.; Robertson, D.W.; Imidazo[4,5-b]pyridines as corticotropin releasing factor receptor ligands. Bioorg Med Chem Lett 2003, 13, 1, 125. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 34269 | 2,4-pyridinediol | 626-03-9 | C5H5NO2 | 详情 | 详情 |
(II) | 40490 | 3-nitro-2,4-pyridinediol | 89282-12-2 | C5H4N2O4 | 详情 | 详情 |
(III) | 63238 | 4-chloro-3-nitro-2-pyridinol | C5H3ClN2O3 | 详情 | 详情 | |
(IV) | 65004 | 02-(benzyloxy)-4-chloro-3-nitropyridine; benzyl 4-chloro-3-nitro-2-pyridinyl ether | C12H9ClN2O3 | 详情 | 详情 | |
(V) | 65003 | 2-chloro-4-(difluoromethoxy)phenylboronic acid | C7H6BClF2O3 | 详情 | 详情 | |
(VI) | 65002 | 2-(benzyloxy)-4-[2-chloro-4-(difluoromethoxy)phenyl]-3-nitropyridine; benzyl 4-[2-chloro-4-(difluoromethoxy)phenyl]-3-nitro-2-pyridinyl ether | C19H13ClF2N2O4 | 详情 | 详情 | |
(VII) | 65005 | 4-[2-chloro-4-(difluoromethoxy)phenyl]-3-nitro-2-pyridinol | C12H7ClF2N2O4 | 详情 | 详情 | |
(VIII) | 65006 | 2-chloro-4-[2-chloro-4-(difluoromethoxy)phenyl]-3-nitropyridine; 3-chloro-4-(2-chloro-3-nitro-4-pyridinyl)phenyl difluoromethyl ether | C12H6Cl2F2N2O3 | 详情 | 详情 | |
(IX) | 65007 | 1-cyclobutyl-1-ethanamine; 1-cyclobutylethylamine | C6H13N | 详情 | 详情 | |
(X) | 65008 | 4-[2-chloro-4-(difluoromethoxy)phenyl]-N-(1-cyclobutylethyl)-3-nitro-2-pyridinamine; N-{4-[2-chloro-4-(difluoromethoxy)phenyl]-3-nitro-2-pyridinyl}-N-(1-cyclobutylethyl)amine | C18H18ClF2N3O3 | 详情 | 详情 | |
(XI) | 65009 | 4-[2-chloro-4-(difluoromethoxy)phenyl]-N~2~-(1-cyclobutylethyl)-2,3-pyridinediamine; N-{3-amino-4-[2-chloro-4-(difluoromethoxy)phenyl]-2-pyridinyl}-N-(1-cyclobutylethyl)amine | C18H20ClF2N3O | 详情 | 详情 |